Glioblastoma multiforme (GBM) represents the most frequently occurring and among the most aggressive form of primary malignant brain tumors, accounting for 54% of glioma. A sub-analysis in an international randomized trial by the European Organization for Research and Treatment of Cancer (EORTC) and the National Cancer Institute of Canada (NCIC) compared the results of radiation therapy (RT) alone with those of concomitant RT and temozolomide (TMZ) and found that the addition of TMZ to RT for newly diagnosed GBM resulted in a significant survival benefit. A significant survival benefit of TMZ administration was also found in the subgroup analysis of the 5-year survival data of the EORTC/NCIC trial. Since then, TMZ has been the first-line chemotherapeutic agent for GBM. However, despite aggressive treatment including surgery, radiation therapy (RT), and adjuvant TMZ-based chemotherapy, the prognosis of patients with GBM has been extremely poor, with a median survival of 14.6 months from diagnosis. The median progression-free-survival (PFS) after standard therapy is 6-9 months, demonstrating that current treatment options are palliative rather than curative.
The Cancer Genome Atlas Network has cataloged recurrent genomic abnormalities in GBM. The Network described a gene expression-based molecular classification of GBM into Proneural, Neural, Classical, and Mesenchymal subtypes and integrated multidimensional genomic data to establish patterns of somatic mutations and DNA copy number. Aberrations and gene expression of EGFR, NF1, PDGFRA/IDH1, and EGFR/neuron markers were used to define the Classical, Mesenchymal, Proneural, and Neural subtypes, respectively. The response of GBM to therapy has been found to differ by subtype.
The prognosis for recurrent glioblastoma (RGBM) is much worse than for GBM, with a majority of patients dying within six months. In general, treatment of RGBM may involve repeated resection, focal RT, chemotherapy or experimental therapies. However, there has been very modest progress in the treatment of RGBM and there are no standard treatment recommendations for RGBM. In view of the unfavorable survival outlook with currently available treatment modalities, new methods for the treatment for GBM and RGBM are desirable.
It should be understood that the various aspects are not limited to the depictions provided in the drawings.